Beginning at age 22, Harris taught school and made his career in St. Louis, Missouri, from 1857 to 1880, a period when the city was growing rapidly.

While in St. Louis, William Torrey Harris implemented many influential ideas to strengthen both the institution of the public school system and the basic philosophical principles of education.

In St. Louis, Harris met mechanic and philosopher Henry Clay Brockmeyer, a German immigrant whose influence turned him toward hegelianism.

With Brockmeyer and other of the St. Louis Hegelians, Harris founded and edited the Journal of Speculative Philosophy (1867); it was the first philosophical periodical in the United States.

Its contributors promoted Hegel's concept of time and events as part of a universal plan, a working out of an eternal historical dialectic.

Harris returned to New England, where he was associated with Amos Bronson Alcott's Concord School of Philosophy in Massachusetts from 1880 to 1889.

In 1889 Harris was appointed as U.S. Commissioner of Education, serving under presidents Benjamin Harrison, Grover Cleveland, William McKinley and Theodore Roosevelt, until 1906.

Harris worked to organize all phases of education on the principles of philosophical pedagogy as espoused by Hegel, Kant, Fichte, Fröbel, Pestalozzi and many others of idealist philosophies.

In an article entitled "An Educational Policy for Our New Possessions", Harris wrote:[5] If the other people of the world to the number of some fourteen hundred millions are united under the five great powers of Europe, while we in turn have only one hundred millions, our national idea will be threatened abroad and have more dangers than ever at home....We must accept the charge of as many of these colonies as come to our hand.

William Torrey Harris took Bacon’s original ideas on the organization of information for libraries and modernized them to be applied in the United States by the second half of the 1800s.

Harris used a deductive hierarchy and created a structure better adapted to the interrelation of knowledge, which facilitated its application in libraries’ catalogs.

Besides voluminous reports on educational matters, many papers contributed to the Proceedings of the American Social Science Association, and various compilations edited by him, his publications include: Harris–Stowe State University in St. Louis is named for Harris, and author Harriet Beecher Stowe.